The first line drugs currently used for the treatment of visceral leishmaniasis are pentavalent antimony compounds such as sodium stibogluconate and meglumine antimoniate. These drugs due to their polar nature are inactive by the oral route and undergo rapid renal excretion following dosing by the parenteral route, which necessitates a multiple dosing regime. Compliance with such a regimen is difficult to achieve in remote areas such as the Sudan where visceral leishmaniasis is endemic and has reached epidemic proportions. Development of a vesicular formulation of such antimonial drugs could increase their efficacy, allowing both the number of doses and dose size to be lowered.
The constituents of a vesicular formulation can influence vesicle characteristics (e.g. stability, size, charge) and hence its suitability as a drug carrier system and depending on the intended usage the requirements of the formulation can be drug specific. In our previous studies using a murine model of visceral leishmaniasis we have shown that vesicle size is important since elimination of Leishmania parasites from deeper sites such as the spleen required the use of small, drug loaded vesicles. Incomplete removal of parasites from these sites results in relapse and probably underlies the 2-8% relapse rate reported after antimonial therapy.
Diverse non-ionic surfactants can be used to form vesicles with potential therapeutic applications such as drug delivery (Ozer et al., 1991) and immunological adjuvants (Brewer and Alexander, 1993). We have already demonstrated (Carter et al., 1989a,b) that stibogluconate loaded non-ionic surfactant vesicles are as effective as drug loaded liposomes for improving the treatment of experimental visceral leishmaniasis.
It is an object of the present invention to provide such a vesicle formulation of improved efficacy. This and other objects of the present invention will become apparent from the following description and examples.